藤黄酸对人结肠癌SW480细胞裸鼠移植瘤生长及血管生成的影响  

Effects of gambogic acid on the growth and angiogenesis of subcutaneous tumor xenografts from human colon cancer cell SW480 in nude mice established

作　　者：梁文龙[1] 曹杰[1] 杨平[1] 李旺林[1] 廖述文 张通[1] 陈熙文[1] 王强[1] 孙政[1] 

机构地区：[1]广州医科大学附属广州市第一人民医院胃肠外科,510180

出　　处：《广东医学》2014年第16期2498-2501,共4页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:81272556);广东省科技计划项目(编号:2010B060900016);广州市医药卫生科技项目(编号:20131A011009)

摘　　要：目的探讨藤黄酸对人结肠癌SW480细胞裸鼠移植瘤生长和肿瘤血管生成的抑制作用及藤黄酸对血管内皮生长因子受体2(VEGFR2)表达的影响,初步探讨藤黄酸抗结直肠癌的作用机制。方法建立人结肠癌SW480细胞裸鼠皮下移植瘤模型,15 d后开始用不同浓度藤黄酸治疗,28 d后处死,测定裸鼠移植瘤的体积和质量,计算其抑瘤率;HE染色观察肿瘤坏死、微血管形态的变化;提取组织中总RNA和蛋白,RT-PCR检测肿瘤组织中VEGFR2 mRNA水平,免疫组织化学法检测肿瘤组织中VEGFR2蛋白表达水平和肿瘤微血管密度(MVD)。结果 (1)对照组,藤黄酸低、中、高剂量组移植瘤体积分别为(691±67.2)、(481±62.9)、(377±37.0)、(190±67.9)mm3,瘤质量分别为(0.681±0.072)、(0.473±0.062)、(0.377±0.044)、(0.192±0.068)g,藤黄酸低、中、高剂量组瘤体积、瘤质量均低于对照组(均P<0.05);藤黄酸低、中、高剂量组抑瘤率分别为31%、45%、72%;(2)HE染色可见藤黄酸组肿瘤组织出现凝固性坏死,肿瘤新生血管闭锁;(3)与对照组相比,藤黄酸组VEGFR2 mRNA表达丰度和蛋白水平明显降低,并呈显著量效关系;(4)对照组MVD明显高于藤黄酸组(P<0.05)。结论藤黄酸能够抑制人结肠癌SW480细胞裸鼠移植瘤的生长,能抑制结肠癌移植瘤内新生血管内皮细胞的生长,其机制可能与抑制VEGFR2的表达有关。[ Abstract] Objective To investigate the inhibitory effects of gambogic acid on the growth, tumor angiogenesis and expression of vascular endothelial growth factor receptor 2 （VEGFR2） of subcutaneous tumor xenografts in nude mice established from human colon cancer cell SW480. Methods A nude mice model of colon cancer was established by sub- cutaneous inoculation of human colon cancer cell line SW480. The mice were treated with different concentrations of gam- bogie acid since the 15th day after transplantation, and were sacrificed on the 28th day. Tumor volume and weight were measured, and the inhibition rate was calculated. HE staining was performed to identify the tumor necrosis and microves- sel morphological changes. The total RNAs and proteins in tumor xenografts were extracted. The mRNA and protein ex- pression of VEGFR2 in tumor xenografts were analyzed by RT - PCR and immunohistochemistry, respectively. The mi- crovessel density （MVD） in tumor xenografts was observed by immunohistochemistry. Results By the end of treatment, the tumor volume of control group, gambogic acid low - , medium - and high - dosage groups were 691 ± 67.2, 481 ± 62. 9, 377 ±37.0 and 190 ± 67.9ram3, respectively ; while the tumor weights were 0. 681 ± 0. 072, 0. 473 ± O. 062, O. 377 ±0. 044 and 0. 192 ±0. 068 g, respectively. Through analysis of variance, the tumor volumes and weights of gam- bogic acid low - , medium - and high - dosage groups were significantly smaller than control group （ all P 〈 0. 05 ） , with inhibition rates of 31%, 45% and 72%, respectively. Coagulation necrosis and neovascularization atresia in tumor were observed in gambogic acid treatment groups. Compared with control group, VEGFR2 mRNA and protein in gambogic acid treatment groups were significantly reduced in concentration - dependent manners （P 〈 0. 05）. The MVD in control group was significantly higher than those in the gambogic acid treatment groups （P 〈 0. 05）. Conclusion Gambogic acid can significantly inhibit the

关 键 词：结肠癌 藤黄酸 SW480细胞 裸鼠移植瘤 新生血管生成 血管内皮生长因子受体2 

分 类 号：R971.1[医药卫生—药品]